chrX-7257367-ACCT-A

Variant names:

• chrX-7257367-ACCT-A
• rs773065157
• NM_001320752.2:c.259+8_259+10delCCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001320752.2(STS):​c.259+8_259+10delCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 1,210,421 control chromosomes in the GnomAD database, including 37 homozygotes. There are 2,775 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., 170 hem., cov: 24)
  • Exomes 𝑓: 0.0075 (33 hom. 2605 hem.)
• Consequence: STS NM_001320752.2 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0360
• Publications: 0 publications found

Genes affected

STS (HGNC:11425): (steroid sulfatase) This gene encodes a multi-pass membrane protein that is localized to the endoplasmic reticulum. It belongs to the sulfatase family and hydrolyzes several 3-beta-hydroxysteroid sulfates, which serve as metabolic precursors for estrogens, androgens, and cholesterol. Mutations in this gene are associated with X-linked ichthyosis (XLI). Alternatively spliced transcript variants resulting from the use of different promoters have been described for this gene (PMID:17601726). [provided by RefSeq, Mar 2016]

STS Gene-Disease associations (from GenCC):

• recessive X-linked ichthyosis

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant X-7257367-ACCT-A is Benign according to our data. Variant chrX-7257367-ACCT-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00579 (651/112431) while in subpopulation NFE AF = 0.00939 (499/53167). AF 95% confidence interval is 0.00871. There are 4 homozygotes in GnomAd4. There are 170 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.259+8_259+10delCCT		splice_region intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.295+8_295+10delCCT		splice_region intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.295+8_295+10delCCT		splice_region intron	N/A	NP_001307680.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.259+5_259+7delCCT		splice_region intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.259+5_259+7delCCT		splice_region intron	N/A	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.259+5_259+7delCCT		splice_region intron	N/A	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 651 AN: 112381 Hom.: 4 Cov.: 24

Gnomad AFR AF: 0.000871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00528

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00182

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00938

Gnomad OTH AF: 0.00199

GnomAD2 exomes AF: 0.00605 AC: 1107 AN: 182866 AF XY: 0.00557

Gnomad AFR exome AF: 0.000914

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00321

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0165

Gnomad NFE exome AF: 0.00882

Gnomad OTH exome AF: 0.00664

GnomAD4 exome AF: 0.00745 AC: 8182 AN: 1097990 Hom.: 33 AF XY: 0.00717 AC XY: 2605 AN XY: 363350

African (AFR) AF: 0.000909 AC: 24 AN: 26402

American (AMR) AF: 0.00168 AC: 59 AN: 35197

Ashkenazi Jewish (ASJ) AF: 0.00392 AC: 76 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00107 AC: 58 AN: 54132

European-Finnish (FIN) AF: 0.0152 AC: 614 AN: 40511

Middle Eastern (MID) AF: 0.00121 AC: 5 AN: 4136

European-Non Finnish (NFE) AF: 0.00841 AC: 7082 AN: 841955

Other (OTH) AF: 0.00573 AC: 264 AN: 46077

GnomAD4 genome AF: 0.00579 AC: 651 AN: 112431 Hom.: 4 Cov.: 24 AF XY: 0.00491 AC XY: 170 AN XY: 34617

African (AFR) AF: 0.000869 AC: 27 AN: 31060

American (AMR) AF: 0.00234 AC: 25 AN: 10671

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 14 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00182 AC: 5 AN: 2746

European-Finnish (FIN) AF: 0.0127 AC: 78 AN: 6150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00939 AC: 499 AN: 53167

Other (OTH) AF: 0.00197 AC: 3 AN: 1525

Alfa AF: 0.00743 Hom.: 57

Bravo AF: 0.00471

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	X-linked ichthyosis with steryl-sulfatase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs773065157; hg19: chrX-7175408;